Certain Bacteria Might Make Type 2 More Likely

Triumphs of technology such as clean water and antibiotics, along with preservatives in food and increased sanitation, have had definite upsides.

ResearcherRuchi Mathur, MD, FRCP(C)

OccupationEndocrinologist, Cedars-Sinai Medical Center

FocusPrediabetes

ADA Research FundingInnovation Grant

But it's possible they've resulted in some unexpected side effects as well—namely, upsetting a balance established over millennia in a matter of decades. A growing number of researchers think that "20th century diseases" virtually unknown to our ancestors—from type 2 diabetes to Crohn's disease and irritable bowel syndrome—are caused in part by changes in the types of bacteria that live in and on us.

That we regularly play host to bacteria and viruses at all may come as a surprise. Yet the human body houses hundreds of different species of microscopic organisms, living in and on our hair and skin, and especially in our digestive system.

There are billions of these little guys: In fact, some estimates suggest 90 percent of the cells in our bodies aren't even human. The complex community of organisms in and on us is called the "microbiome."

As far as we know, most of these species are just along for the ride. Some are harmful, such as the bacteria in your mouth that cause cavities. And still others actively help our cells with vital tasks such as digestion and producing vitamins. "We're vehicles for their preservation and growth," says Ruchi Mathur, an endocrinologist at Cedars-Sinai Medical Center in Los Angeles. "There's evidence that humans have coevolved with these organisms for millions of years."

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Mathur is particularly interested in the idea that the microflora in the gut could contribute to type 2 diabetes. "We wanted to see if there is a specific organism involved in glucose metabolism and obesity," she says. "We think the microbiota is one piece of the puzzle that contributes to diabetes and obesity."

Her top suspect is Methanobrevibacter smithii, one of the many microscopic inhabitants of the human digestive system. It's thought to work with other microorganisms in the gut to make the most of food. "M. smithii helps other microorganisms harvest more energy," Mathur says, meaning that people with more M. smithii manage to extract more calories from the same amount of food compared to people with less, perhaps contributing to overweight and obesity. One way to detect higher levels of M. smithii is a breath test—the organism produces methane gas in small quantities.

Studies have already shown that M. smithii is associated with obesity. In a study of people undergoing gastric bypass surgeries, patients who had detectable levels of methane in their breath had body mass indexes an average of 7 points higher than the rest of the people in an already obese group. A clue to the reasons why may come from animal research. In studies of dogs, there was a marked slowing down of food through their digestive tracts after methane was introduced as part of an experiment. It's possible that microorganisms making methane in the small intestine have the same effect, increasing the time food spends in the digestive system and thus the calories extracted with the help of microorganisms.

With the help of a grant from the American Diabetes Association, Mathur is working to confirm the link between M. smithii, obesity, and prediabetes by taking a look at how efficiently people digest food with and without the organism's help. First, prospective participants—all of whom are overweight or obese and show the elevated blood glucose levels of prediabetes—are given a breath test to look for traces of methane.

Next, they will be given a standard diet over the course of three days. Mathur's team will give the participants a "smart pill" to swallow that tracks how fast the food moves through the gut and will measure what comes out the other end. "If we know the calories of what they're eating and what comes out, we can determine the calorie harvest by subtracting," she says.

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Then the whole process will be repeated, this time with a crucial difference: a course of an antibiotic, which does not enter the bloodstream, to wipe out the M. smithii in each participant's intestines. By comparing the "before" and "after" calorie harvesting of each person's digestive tract, Mathur hopes to find out just how many more calories the methane-producing M. smithii squeezes out of meals.

The aim of research like Mathur's is a more complete understanding of the incredibly complex microscopic communities we carry around with us. "If you could manipulate the gut flora," using designer drugs, probiotic nutrition supplements, or targeted antibiotics, "that would be the ultimate goal," Mathur says of the search for new ways to treat obesity and prediabetes.